Parathyroid Cystic Adenoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To review diagnostic imaging modalities for parathyroid cystic adenomas (PCA). Since PCAs are a rare (0.5%-1%) subclass of parathyroid adenomas, and due to their cystic component, imaging modalities known to be efficient for diagnosing solid adenomas might fail in localizing them. METHODS: We conducted a systematic review using the PubMed and Cochrane databases for English articles on PCAs published between 1995 and 2020. A meta-analysis of the retrieved data was performed. RESULTS: Overall, 39 studies, reporting on a total of 160 patients, were included in the analysis. Two thirds (68%) of the patients were female, with a mean age of 53.9 years. A single cystic adenoma was detected in 98.1% of cases. The mean blood calcium corrected for albumin level was 12.6 ± 2.7 mg/dL, and the mean parathyroid hormone level was 565.5 ± 523.8 pg/mL. The mean PCA sizes as measured by ultrasound (US), computed tomography (CT), and ex vivo measurement were 4.8 ± 3.6, 5.2 ± 3.2, and 3.5 cm, respectively. The median weight was 8.1 g. PCA was detected in 86% of US examinations; 100% of US-guided fine needle aspiration, 4-dimensional computed tomography (4D-CT), or magnetic resonance imaging examinations; and 61% of 99m-technetium sestamibi scan with single-photon emission computed tomography ((99m)Tc-SPECT). (99m)Tc-SPECT showed a significantly lower diagnostic rate than US (odds ratio, 3.589), US-guided fine needle aspiration, CT combined with 4D-CT, and the combination of US, CT, 4D-CT, and magnetic resonance imaging (P < .001). CONCLUSION: Although US and 4D-CT showed a significantly high rate in diagnosing PCA, (99m)Tc-SPECT showed a lower PCA diagnostic rate. These findings suggest that larger cystic lesions suspected as PCAs should be further evaluated using 4D-CT rather than (99m)Tc-SPECT.

Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue.

Diagnosis of primary hyperparathyroidism (PHP) is based on blood assessments in terms of synchronous high calcium and PTH (parathormone), but further management, particularly parathyroid surgery that provides the disease cure in 95-99% of cases, requires an adequate localisation of the parathyroid tumour/tumours as the originating source, with ultrasound and 99m-Technetium (99m-Tc) sestamibi scintigraphy being the most widely used. We aimed to introduce an adult female case diagnosed with PHP displaying unexpected intra-operatory findings (ectopic thyroid tissue) in relation to concordant pre-operatory imaging modalities (ultrasound + dual-phase 99m-Tc pertechnetate and sestamibi scintigraphy + computed tomography) that indicated bilateral inferior parathyroid tumours. A sudden drop in PTH following the removal of the first tumour was the clue for performing an extemporaneous exam for the second mass that turned out to be non-malignant ectopic thyroid tissue. We overviewed some major aspects starting from this case in point: the potential pitfalls of pre-operatory imaging in PHP; the concordance/discordance of pre-parathyroidectomy localisation modalities; the need of using an additional intra-operatory procedure; and the clues of providing a distinction between pathological parathyroids and thyroid tissue. This was a case of adult PHP, whereas triple localisation methods were used before parathyroidectomy, showing concordant results; however, the second parathyroid adenoma was a false positive image and an ectopic thyroid tissue was confirmed. The pre-operatory index of suspicion was non-existent in this patient. Hybrid imaging modalities are most probably required if both thyroid and parathyroid anomalies are suspected, but, essentially, awareness of the potential pitfalls is mandatory from the endocrine and surgical perspectives. Current gaps in imaging knowledge to guide us in this area are expected to be solved by the significant progress in functional imaging modalities. However, the act of surgery, including the decision of a PTH assay or extemporaneous exam (as seen in our case), represents the key to a successful removal procedure. Moreover, many parathyroid surgeons may currently perform 4-gland exploration routinely, precisely to avoid the shortcomings of preoperative localisation.

The prevalence and significance of nonuniform thyroid radio-isotope uptake in patients with Graves' disease.

OBJECTIVE: To evaluate the prevalence and clinical significance of nonuniform technetium (99m Tc) uptake among patients with Graves' disease (GD). DESIGN, PATIENTS AND MEASUREMENTS: Patients with GD, referred between July 2005 and March 2018, had Tc99 - uptake scans and TSH-receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns. RESULTS: Of the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4 pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 - 1.10). The risk of relapse was similar in both groups after a median (IQR) follow-up of 41 (13-74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96-3.15). CONCLUSIONS: Nonuniform radio-isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio-isotope uptake with ATD therapy as first-line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio-labelled uptake scans being reserved for those who are TRAb negative.

Application value of contrast-enhanced ultrasound in preoperative localization of microwave ablation for primary hyperparathyroidism.

BACKGROUND: Ultrasonography (US) and 99m Technetium-sestamibi scintigraphy (99m Tc-MIBI) are currently first-line imaging modalities to localize parathyroid adenomas with sensitivities of 80% and 84%, respectively. Therefore, finding other modalities to further improve the diagnostic accuracy for preoperative localization is critically needed. PURPOSE: To evaluate the application value of contrast-enhanced ultrasound (CEUS) in the preoperative localization of microwave ablation (MWA) for primary hyperparathyroidism (PHPT). METHODS: Between December 2012 and May 2021, 100 PHPT patients (34 males and 66 females; mean age, 56.31 ± 13.43 years; age range, 25-85 years) with 130 suspected parathyroid nodules were enrolled. US, CEUS, and 99m Tc-MIBI were performed for the localization of pathological parathyroid glands. All patients were performed MWA under ultrasound guidance. All the suspected parathyroid nodules underwent core needle biopsy under ultrasound guidance during MWA to confirm the pathology. The diagnostic performance of all the imaging tests was analyzed in comparison with the pathological results. RESULTS: A total of 130 nodules suspected to be of parathyroid origin from preoperative localization images were confirmed by pathological results, of which 116 were of parathyroid origin, and 14 were not of parathyroid origin. The sensitivity, specificity, accuracy, and the area under receiver operating characteristic curve of CEUS in the localization of pathological parathyroid glands were 100%, 92.86%, 99.23%, and 0.964, which were significantly higher than those of US (93.10%, 42.86%, 87.69%, and 0.680) and 99m Tc-MIBI (81.90%, 42.86%, 77.69%, and 0.624) (p < 0.05). The sensitivity and accuracy of CEUS were 100% and 97.22%, which were higher than those of 99m Tc-MIBI (65.62% and 63.89%) or US (75.00% and 72.22%) in patients with multiple parathyroid glands (p < 0.05). For smaller parathyroid adenomas (≤2 cm in diameter), the sensitivities of CEUS in locating hyperfunctioning parathyroid glands were 100%, which was significantly higher than that of 99m Tc-MIBI (73.68% and 84.31%, p < 0.05). CONCLUSIONS: CEUS is a valuable preoperative localization method for PHPT patients performed MWA, especially for the patients with smaller pathological parathyroid gland and multiple glandular lesions.

Reduced urinary excretion of neutrophil gelatinase-associated lipocalin as a risk factor for recurrence of febrile urinary tract infection in children.

BACKGROUND: This study aimed to test the hypothesis that reduced urinary excretions of neutrophil gelatinase-associated lipocalin (NGAL) predispose children to recurrence of febrile urinary tract infection (fUTI). METHODS: Subjects were 38 children diagnosed with fUTI. To examine risk factors for recurrence of fUTI, the subjects were divided into a non-recurrent group and a recurrent group according to the presence or absence of fUTI over 3 years since the first episode. We measured the urinary NGAL levels in patients with fUTI at the non-infected stage in addition to age-matched healthy control children. RESULTS: In a multiple logistic regression analysis, significant differences between the groups were not observed for age, sex, the prevalence of kidney scarring and bladder bowel dysfunction, urinary ß2-microglobulin/creatinine (Cr) level, and serum levels of Cr and Cystatin C, while the recurrent group had significantly more cases with grade III or higher vesicoureteral reflux (p < 0.01). Furthermore, the urinary NGAL/Cr in the recurrent group (median, 3.60 µg/gCr) was significantly lower than that in the non-recurrent group (median, 16.47 µg/gCr; p < 0.01), and age-matched healthy control children (median, 14.14 µg/gCr; p < 0.05). The area under the receiver operating characteristic curve of NGAL/Cr was 0.86 for predicting recurrence of fUTI. A cut-off value of 11.59 µg/gCr had the best accuracy to predict recurrent fUTI yielding a specificity of 78% and a sensitivity of 93%. CONCLUSIONS: Reduced levels of urinary NGAL, which protects against urinary infection, are a risk factor for recurrence of fUTI and could serve as a biomarker.

Enhanced oral bioavailability and biodistribution of atractylodin encapsulated in PLGA nanoparticle in cholangiocarcinoma.

Atractylodes lancea (Thunb) DC. and its bioactive compound atractylodin (ATD), have been shown to exert promising anticancer activity against cholangiocarcinoma (CCA) both in vitro and in vivo. However, the clinical development of ATD could be hindered due to hydrophobicity and poor pharmacokinetic properties, and thus, the requirement of high dose administration and the risk of toxicity. In the present study, ATD-loaded in PLGA nanoparticles (ATD-PLGA) and that coated with chitosan (ATD-PLGA-CS) were developed using nanoprecipitation and single emulsification methods, respectively. The optimized ATD-PLGA formulation provided superior physical and pharmaceutical properties over ATD-PLGA-CS. The antiproliferative activity of ATD-PLGA against the two CCA cell lines, HuCCT1 and CL6, and the normal cell line (OUMS-36T-1F) was evaluated using MTT assay. Results showed that normal epithelial cell was less sensitive to ATD-PLGA compared to both CCA cell lines. In mice, the radiolabelled 99m Tc-ATD-PLGA showed superior pharmacokinetic profile over free 99m Tc-ATD, as evidenced by a 2.7-fold increase of area under plasma concentration-time curve (AUC0-∞ ), maximum plasma concentration (Cmax ), time to Cmax (tmax ), and mean residence time (MRT). Higher accumulation of 99m Tc-ATD-PLGA was observed in vital organs/tissues such as blood, liver, heart, and kidney, compared with free 99m Tc-ATD-PLGA. Altogether, the results suggest that PLGA NPs could be a suitable drug delivery carrier for ATD in CCA.

Wheat gluten intake increases the severity of experimental colitis and bacterial translocation by weakening of the proteins of the junctional complex.

Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and ß-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.

Asymptomatic adult intrapericardial diaphragmatic hernia detected on cardiac SPECT CT.

An 83-year-old man underwent exercise stress test with single photon emission computed tomography (SPECT) myocardial perfusion imaging for new electrocardiogram (EKG) changes. The stress EKG did not show any significant changes. Myocardial perfusion imaging with SPECT demonstrated an inferior wall defect and extracardiac uptake of nuclear tracer. Simultaneous cardiac computed tomography performed for attenuation correction showed presence of intrapericardial hepatic tissue in an anterior diaphragmatic hernia. The herniated tissue was noted to influence the perfusion image and cause the defect. To date, this is a unique finding based on review of literature.

Evaluation of the diagnostic accuracy of skeletal scintigraphy in lame and poorly performing sports horses.

Skeletal scintigraphy is an established imaging modality, however, its validity as a diagnostic test in lame or poorly performing sports horses has not been determined. The objective of this retrospective cross-sectional analytical study was to determine the accuracy of skeletal scintigraphy as an indiscriminate screening test in sports horses. All sports horses that underwent scintigraphic examination between March 2008 and December 2014 for which a definitive diagnosis was reached were included. Examinations were evaluated blindly. Characteristics of increased radiopharmaceutical uptake were recorded and subjectively categorized as possibly relevant or non-relevant. Kappa statistics were used to assess agreement between test results and final diagnosis. There were 1222 positive clinical diagnoses in 480 horses, of which 687 regions (56.4%) had no associated increased radiopharmaceutical uptake and 99 regions (8.1%) had non-relevant increased radiopharmaceutical uptake. The sensitivity of increased radiopharmaceutical uptake for identification of final diagnosis was low (43.8%) and specificity was high (94.0%). The agreement was fair (κ = 0.36). Relevance categorization improved the test; the sensitivity for final diagnosis was low (35.7%), specificity was high (98.9%), and the agreement was moderate (κ = 0.45). The agreements of increased radiopharmaceutical uptake and relevance categorization with final diagnosis were only substantial for feet (κ = 0.67 and κ = 0.66, respectively) and proximal aspect of the forelimb (elbow, shoulder, and scapula combined) (κ = 0.69 and 0.78, respectively). Scintigraphic examination is unlikely to lead to a full and correct diagnosis of the cause(s) of lameness or poor performance in sports horses when used as an isolated or indiscriminate screening tool.

Evaluation of the diagnostic accuracy of skeletal scintigraphy for the causes of front foot pain determined by magnetic resonance imaging.

There is good correlation between increased radiopharmaceutical uptake anywhere in the feet of sports or leisure horses and the presence of foot pain. However, low sensitivity of scintigraphy for identifying lesions contributing to foot pain as determined by magnetic resonance imaging (MRI) has been reported. The aim of this retrospective, cross-sectional, analytical study was to assess the accuracy of scintigraphy for identifying the cause(s) of foot pain, using MRI as the reference standard. Sports and leisure horses that underwent both skeletal scintigraphy and MRI of the front feet between March 2008 and December 2014 and for which a definitive diagnosis of the cause(s) of front foot pain was reached were included (121 feet of 70 horses). Imaging studies were evaluated retrospectively, blindly. Agreements between scintigraphic localization of increased radiopharmaceutical uptake and subjective categorization of lesions with MRI diagnosis were assessed using Kappa statistics (κ). Measures of diagnostic accuracy were calculated. Sensitivity of increased radiopharmaceutical uptake varied among regions (31.8-76.2%) but specificity was at least high for all (84.6-100%). Agreements between both scintigraphy measures and MRI diagnosis were substantial for the distal phalanx (palmar processes and body) (κ = 0.77 and κ = 0.74, respectively), and ungular cartilages and chondral ligaments (κ = 0.62, for both). When all regions were combined, agreements of increased radiopharmaceutical uptake (κ = 0.49) and relevance categorization (κ = 0.45) with MRI diagnosis were moderate. In conclusion, skeletal scintigraphy does not meet the minimum reliability level for a diagnostic test, but is reliable for identification of osseous trauma to the distal phalanx and ungular cartilages.

Gamma scintigraphy and biodistribution of (99m)Tc-cefotaxime sodium in preclinical models of bacterial infection and sterile inflammation.

(99m)Tc-cefotaxime sodium ((99m)Tc-CEF) was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose, and reducing agent type. Labeling studies were performed by changing the selected parameters one by one, and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Simple method for radiolabeling of CEF with (99m)Tc has been developed and standardized. Labeling efficiency of (99m)Tc-CEF was assessed by both radio thin-layer chromatography and radio high-performance liquid chromatography and found higher than 90%. The labeled compound was found to be stable in saline and human serum up to 24 h. Two different freeze dry kits were developed and evaluated. Based on the data obtained from this study, both products were stable for 6 months with high labeling efficiency. The prepared cold kit was found sterile and pyrogen free. The bacterial infection and sterile inflammation imaging capacity of (99m)Tc-CEF was evaluated. Based on the in vivo studies, (99m)Tc-CEF has higher uptake in infected and inflamed thigh muscle than healthy thigh muscle.

Topical delivery of fluorescence (6-Cf) labeled and radiolabeled (99m-Tc) cisplatin and imiquimod by a dual drug delivery system.

The present investigation deals with the development of topical (top.) formulation for co-delivery of cisplatin and imiquimod to enhance the antitumor efficacy of the drug for skin-cited malignancies even in immune compromised patient. Cisplatin (CDDP) and imiquimod-loaded protransfersome gel (CDDP-Imi-Pts gel) formulation was characterized for entrapment efficiency, pH, and viscosity. Further, fluorescence-labeled (6-carboxyfluorescin) and radiolabeled ((99m) technetium) drug-loaded formulations were compared with respect to biodistribution and pharmacokinetic studies. Gamma scintigraphy of mice following radiolabeled formulation administrations was performed to accomplish the localization of drugs in various organs. The percentage entrapment efficiency of cisplatin and imiquimod in the protransfersome gel formulations were found to be 36.22 ± 6.41 and 63.11 ± 3.73. The skin/blood localization ratio of 1.096, 120.13, 0.174, and 349.88 was found for intraperitoneal radiolabeled drug solution ((99m-)Tc-CDDP-Imi-Sol), top. radiolabeled drug-loaded protransfersome gel formulation ((99m-)Tc-CDDP-Imi-Pts gel), intraperitoneal 6-carboxyfluorescin labeled drug solution (6-Cf-CDDP-Imi-Sol), top. 6-carboxyfluorescin labeled drug-loaded protransfersome gel formulation (6-Cf-CDDP-Imi-Pts gel), respectively after 0.5h of administration. CDDP-Imi-Pts gel has a potential for site specific delivery and reduces the systemic toxicity of anti cancer drugs. These findings suggest that the cisplatin-imiquimod co-delivery offers an attractive, novel approach for treatment of skin-cited malignancies.

(99m) Tc-Doxycycline hyclate: a new radiolabeled antibiotic for bacterial infection imaging.

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new (99m) Tc-labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by (99m) Tc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen-free, and stable up to 6 months. Static images depicted rapid distribution throughout the body and high uptake in bacterial infected thigh muscle. The uptake ratios of radiopharmaceuticals in infected thigh muscle were found above 2 up to 5 h. Five hours after injection, the rats were sacrificed, and biodistribution was determined. Samples of bacterial infected muscle, healthy muscle, blood, liver, spleen, lung, kidney, stomach, intestine, urine and heart were weighed, and the radioactivity was measured by using a gamma counter. The %ID/g of (99m) Tc-DOX was found 0.23 ± 0.06 for infected thigh muscle. According to the imaging, biodistribution, and histopathological studies, the promising characteristics of (99m) Tc-DOX make the new radiopharmaceutical valuable to examine for future studies.

Use of Indocyanine Green Near-Infrared Imaging for Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Pilot Study.

PURPOSE: The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99mtechnetium-labeled nanosized colloids (99mTc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC). METHODS: Single-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques (99mTc and ICG) were performed. We injected 99mTc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol. RESULTS: In all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99mTc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases. CONCLUSIONS: Our study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

Evaluating pediatric ureteropelvic junction obstruction: Dynamic magnetic resonance urography vs renal scintigraphy 99m-technetium mercaptoacetyltriglycine.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is a common congenital urinary tract disorder in children. It can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic occurrence. AIM: To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography (dMRU) and scintigraphy 99m-technetium mercaptoacetyltriglycine (MAG-3) for the functional evaluation of UPJO. METHODS: Between 2016 and 2020, 126 patients with UPJO underwent surgery at Robert Debré Hospital. Of these, 83 received a prenatal diagnosis, and 43 were diagnosed during childhood. Four of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging evaluation. Split renal function was evaluated preoperatively using scintigraphy MAG-3 (n = 28), dMRU (n = 53), or both (n = 40). In this study, we included patients who underwent surgery for UPJO and scintigraphy MAG-3 + dMRU but excluded those who underwent only scintigraphy MAG-3 or dMRU. The patients were divided into groups A (< 10% discrepancy) and B (> 10% discrepancy). We examined the discrepancy in split renal function between the two modalities and investigated the possible risk factors. RESULTS: The split renal function between the two kidneys was compared in 40 patients (28 boys and 12 girls) using scintigraphy MAG-3 and dMRU. Differential renal function, as determined using both modalities, showed a difference of < 10% in 31 children and > 10% in 9 children. Calculation of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both kidneys. CONCLUSION: Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UPJO.

Impact of Anti-Mycotic Drugs on the Osteogenic Response of Bone Marrow Mesenchymal Stem Cells In Vitro.

The treatment of fungal bone infections and infected non-unions is a huge challenge in modern trauma and orthopedics, which normally contain the local and systemic administration of anti-fungal drugs. Although frequently used, little is known about the impact of systemic and locally administered fungicides on the osteogenic regenerative capabilities of infected bone tissue, especially upon the osteogenesis of human bone marrow mesenchymal stem cells (BM-hMSCs). This study evaluates the effects of the three most common fungicides for the systemic treatment of bone infections, Voriconazole (VOR), liposomal Amphotericin B (LAMB), and Fluconazole (FLU), as well as the effects of VOR and LAMB-loaded Polymethylmethacrylate (PMMA) cement chips in different concentrations upon the osteogenic response of BM-hMSCs in vitro. Within this study, we compared the ability of BM-hMSC to differentiate into osteoblast-like cells and synthesize hydroxyapatite as assessed by radioactive 99mTechnetium-Hydroxydiphosphonate (99mTc-HDP) labeling, cell proliferation, and analyses of supernatants upon various osteogenic parameters. Our results revealed that VOR added to the cell culture medium affects the osteogenic potential of BM-hMSC negatively, while there were no detectable effects of LAMB and FLU. Moreover, we showed dose-dependent negative effects of high- and extended-dose fungicide-loaded PMMA cement due to cytotoxicity, with a higher cytotoxic potential of VOR than LAMB, while low-dose fungicide-loaded PMMA had no significant effect on the osteogenic potential of BM-hMSC in vitro.

Diagnostic accuracy of renal pelvic dilatation for detecting surgically managed ureteropelvic junction obstruction.

PURPOSE: In this study we evaluate the diagnostic accuracy of renal pelvic dilatation for detecting infants with prenatal hydronephrosis who will need surgical intervention for ureteropelvic junction obstruction during followup. MATERIALS AND METHODS: Between 1999 and 2010, 371 newborns diagnosed with isolated prenatal hydronephrosis were prospectively followed. The main event of interest was the need for pyeloplasty. Diagnostic odds ratio, sensitivity, specificity and diagnostic accuracy (assessed by AUC) of fetal renal pelvic dilatation and postnatal renal pelvic dilatation were evaluated. RESULTS: A total of 312 patients were included in the analysis and 25 (7.5%) infants underwent pyeloplasty. The diagnostic performance for detecting the need for pyeloplasty was excellent for all ultrasonography measurements. The AUC was 0.96 (95% CI 0.92-0.98) for fetal renal pelvic dilatation, 0.97 (95% CI 0.95-0.98) for postnatal renal pelvic dilatation and 0.95 (95% CI 0.92-0.97) for the Society for Fetal Urology grading system. A cutoff of 18 mm for fetal renal pelvic dilatation and a cutoff of 16 mm for postnatal renal pelvic dilatation had the best diagnostic odds ratio to identify infants who needed pyeloplasty. Considering a diagnosis to be positive only if fetal renal pelvic dilatation was greater than 18 mm and postnatal dilatation was greater than 16 mm, sensitivity was 100% and specificity was 86% (95% CI 80.7-89.9). CONCLUSIONS: Our findings suggest that the combination of fetal and postnatal renal pelvic dilatation is able to increase the diagnostic accuracy for detecting infants who need a more comprehensive postnatal investigation for upper urinary tract obstruction.

Novel cancer-targeting SPECT/NIRF dual-modality imaging probe (99m)Tc-PC-1007: synthesis and biological evaluation.

Synthesis, characterization, in vitro and in vivo biological evaluation of a heptamethine cyanine based dual-mode single-photon emission computed tomography (SPECT)/near infrared fluorescence (NIRF) imaging probe (99m)Tc-PC-1007 is described. (99m)Tc-PC-1007 exhibited preferential accumulation in human breast cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of (99m)Tc-PC-1007 was performed in a breast cancer xenograft model. The probe uptake ratio of tumor to control (spinal cord) was calculated to be 4.02±0.56 at 6 h post injection (pi) and 8.50±1.41 at 20 h pi (P<0.0001). Pharmacokinetic parameters such as blood clearance and organ distribution were assessed.

Automatic healthy liver segmentation for holmium-166 radioembolization dosimetry.

BACKGROUND: For safe and effective holmium-166 (166Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166Ho and technetium-99m stannous-phytate accumulating in healthy liver cells (166Ho-99mTc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99mTc images derived from a 166Ho-99mTc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99mTc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166Ho SPECT to compute absorbed dose in healthy liver. RESULTS: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity. CONCLUSIONS: 166Ho-99mTc dual-isotope protocol can automatically segment the healthy liver without hampering the 166Ho dosimetry assessment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988.

99mTechnetium-Ubiquicidin Scan with Single-Photon Emission Computed Tomography/Computed Tomography in Skull Base Osteomyelitis.

Malignant otitis externa (MOE) with skull base osteomyelitis (SBO) is an aggressive infection that predominantly affects elderly, diabetic, or immunocompromised patients, and is associated with high disease-specific mortality. Pseudomonas aeruginosa is the most isolated microorganism. External otitis associated with granulation tissue and pain is the most common presenting feature; a biopsy is obtained to rule out malignancy. A proper consensus is lacking regarding the best imaging modality for early initial diagnosis and follow-up. 99mTechnetium (99mTc)-labeled ubiquicidin (UBI) 29-41 is a bacterial attaching peptide that does not bind to activated leukocytes. We report a case of SBO initially misdiagnosed as a chronic otitis media, but later proved to be a case of MOE. 99mTc methylene diphosphonate bone scan and 99mTc-UBI 29-41 scan with single-photon emission computed tomography/computed tomography scans were performed to corroborate the clinical diagnosis. SBO remains a great challenge due to its increasing prevalence and high morbidity are difficult to diagnose and are often confused with cholesteatoma and neoplastic process. The UBI scan could be an auxiliary noninvasive diagnostic alternative in early diagnosis.